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151.
目的:以汉防己甲素和汉防己乙素的提取率作为考察指标,优化防己中汉防己甲素和汉防己乙素的提取工艺。方法:利用高效液相色谱法测定汉防己甲素和汉防己乙素的含量,采用响应曲面法考察乙醇体积分数、料液比及超声时间对提取效果的影响。结果:Design expert 10预测得到汉防己甲素最佳提取工艺为乙醇浓度为60%,料液比为1∶36.07,超声时间为57.12 min,提取率为13.53 mg/g;最佳提取汉防己乙素的提取工艺为乙醇浓度62.49%,料液比为1∶37.71,超声时间为59.38 min,提取率为8.71 mg/g。结论:该研究为防己中防己甲素和汉防己乙素的提取工艺提供实验依据。 相似文献
152.
目的:研究粉防己碱(Tet)对猪冠状动脉平滑肌细胞(SMC)钙激活钾通道(K_(Ca))的作用。方法:用膜片钳单通道技术确定通道的变化。结果:Tet 浓度依赖性地可逆性阻断 SMC 上的 K_(Ca)。细胞膜内侧面加入 Tet 20、30×10~(-6)mol·L~(-1)可分别使通道开放概率降低(58.2±20.3)%、(64.6±16.6)%,平均开放时间从(2.3±0.7)ms 减少到(2.0±0.8)ms 和(1.6±0.6)ms,平均关闭时间从(68.1±39.3)ms 减少到(64.0±62.4)ms 和(37.0±16.6)ms。随 Tet 浓度的增加,通道活动逐步完全抑制。结论:Tet 是一种天然有效的SMC 上 K_(Ca)抑制剂。 相似文献
153.
目的探讨粉防己碱对缺血-再灌注损伤大鼠心肌细胞凋亡及Bcl-2/Bax蛋白表达的影响。方法结扎大鼠左冠状动脉前降支(LAD)30min后松开,再灌注24h建立心肌缺血-再灌注损伤模型。将48只雄性SD大鼠随机分为:假手术组(Sham组),缺血-再灌注损伤组(IRI组),粉防己碱预处理组(Tet组)。再灌注结束后检测血清肌酸激酶同工酶MB(CK-MB)和心肌梗死范围(IS/AAR,%)。应用原位末端标记法(TUNEL法)检测各组凋亡细胞,计算凋亡指数(AI),应用免疫组化法检测心肌Bcl-2、Bax蛋白表达,计算Bcl-2/Bax值,进行组间比较。结果与IRI组相比,Tet可明显降低CK-MB值(976.57±160.69)vs(1910.38±221.10)U/L,P〈0.01,减小心肌IS/AAR%,(23.28±4.38)%vs(43.76±6.30)%,P〈0.01。与IRI组比较,粉防己碱预处理可显著减少心肌细胞凋亡,AI显著降低(8.62±2.45%vs19.36±5.28%,P〈0.01)。粉防己碱预处理使Bcl-2表达增加,Bax表达下降,Bcl-2/Bax值显著升高(P〈0.01)。结论粉防己碱能明显抑制缺血-再灌注损伤引起的心肌细胞凋亡,其作用机制可能与促进Bcl-2蛋白表达,减少Bax蛋白表达、升高Bcl-2/Bax比值有关。 相似文献
154.
目的为评价汉防己甲素(TET)应用于神经母细胞瘤的可能性,应用TET处理人神经母细胞瘤株TGW,观察其作用情况。方法采用MTT比色法观察TET对神经母细胞瘤增生的影响,琼脂凝胶电泳法观察DNA片断化的梯形条带,流式细胞仪观察TET对神经母细胞瘤凋亡水平影响,实时定量PCR法了解Bcl_2家族(Bcl_2,Bcl_XL,Bad,Bax)表达的变化。结果25~0.5μMTET能明显抑制TGW细胞,25μM汉防己甲素作用48h最大抑制率为(95.32±2.46)%;琼脂糖凝胶电泳法观察到25μMTET处理12、24、36、48h后出现典型的凋亡表现;流式细胞仪Annexin及PI双染发现25μMTET孵育24h肿瘤细胞的凋亡率明显上升;实时定量PCR发现25μMTET处理24h后Bax基因表达明显增加。结论汉防己甲素能诱导人神经母细胞瘤株TGW凋亡,上调Bax基因的表达。 相似文献
155.
目的 探讨汉防己甲素(Tetrandrine,Tet)对急性脊髓损伤(Acute spinal cord injuries,ASCI)的保护作用。方法 74只Wistar大鼠随机分为4组,用改良Allen’s打击法制备大鼠截瘫模型,造模前各组分别投给相应的药物,伤后1h、4h取损伤区脊髓组织进行形态学观察和生化指标测定。结果 汉防己甲素能明显降低组织钙总量和MDA含量,防止镁总量和SOD含量的下降,稳定6-Keto-PGFla/TXB2的比值,减轻组织病损。结论 Tet对ASCI有保护作用,其作用机制为①扩张微血管,改善微循环,逆转ASCI后早期缺血倾向;②抗氧自由基,减轻组织过氧化损伤,稳定生物膜性结构;③减少ASCI后钙内流,从而阻断继发性损伤的链式反应。 相似文献
156.
目的:探讨最大非毒性剂量汉防己甲素(tetrandrine,Tet)对人鼻咽癌细胞株CNE1和CNE2的放疗增敏机制。方法:分别采用最大非毒性剂量Tet(对CNE1细胞为1.5μmol/L;对CNE2细胞为1.8μmol/L)、4 Gy放疗和最大非毒性剂量Tet联合放疗处理CNE1和CNE2细胞;流式细胞术检测各组细胞周期分布,Western blot检测各组细胞γ-H2AX、cleaved caspase-3、p-CDC25C、CDK1、p-CDK1、cyclin B1、ERK和p-ERK的蛋白水平。结果:最大非毒性剂量Tet联合放疗后可上调CNE1和CNE2细胞中γ-H2AX的表达。放疗组CNE1和CNE2细胞G_2/M期的比例分别为(18.09±0.42)%和(18.48±1.32)%,联合处理组CNE1和CNE2细胞G_2/M期的比例降为(15.88±1.04)%和(13.80±0.82)%,与放疗组比较差异有统计学意义(P0.05)。联合处理可增加放疗所致的cleaved caspase-3的蛋白水平(P0.05)。不同浓度Tet处理CNE1和CNE2细胞后,p-CDC25C和p-CDK1的蛋白水平随Tet浓度增加而升高(P0.05),CDK1的表达无明显改变;最大非毒性剂量Tet不影响p-CDC25C、p-CDK1和CDK1的蛋白水平。在CNE1和CNE2细胞中,联合处理可明显降低放疗引起的p-CDC25C和p-CDK1的蛋白水平(P0.05),上调放疗后cyclin B1的表达,而对总CDK1的表达无明显调节作用;联合处理可显著抑制放疗所致的pERK蛋白水平(P0.05)。结论:最大非毒性剂量Tet可以增加放疗引起的CNE1和CNE2细胞的DNA断裂及细胞凋亡,其放疗增敏的机制可能与Tet调控ERK/CDC25C/CDK1/cyclin B1通路、去除放疗导致的G2/M期阻滞有关。 相似文献
157.
Chang Xu Zhongxian Chen Yuanxiang Wang Zhongxun Xiong Yi Ji 《Journal of pediatric surgery》2009,44(8):1611-405
Purpose
Tetrandrine (Tet) is a bisbenzylisoquinoline alkaloid isolated from the root of Stephania tetrandra, which has been used in traditional Chinese medicine to treat patients with silicosis, asthma, and pulmonary hypertension, and others and can be used as a pulmonary therapeutic agent. We hypothesized that it can also improve the lung growth in congenital diaphragmatic hernia (CDH) for its multiple biological effects. There are increasing evidences that suggest transforming growth factor β1(TGF-β1) plays a crucial role in fetal lung growth and morphogenesis. The aim of this study was to evaluate the effect of prenatal administration of Tet and to investigate its possible mechanism on the expression of TGF-β1 in the lung of nitrofen-induced CDH rat model.Methods
A CDH model was induced in pregnant Sprague-Dawley rats by administration of nitrofen on day 9.5 of gestation (Ed9.5 term, day 22). Tetrandrine (30 mg/kg) was given through gavage (once a day, for 3 days) on Ed11.5. Accordingly, there were 3 groups as follows: control (n = 9), CDH (n = 9), and CDH + Tet (n = 9). All the fetuses were delivered by cesarean delivery on Ed16.5, 18.5, and 21.5, respectively, to check if diaphragmatic hernia existed on each fetus, then the lung tissue weight (LW) and body weight (BW) of each fetus were recorded. Histologic evaluations and TGF-β1 immunohistochemistry staining in the lung sample were performed for image analysis.Results
Diaphragmatic hernia was observed in 95 of the 112 rat fetuses in CDH and CDH + Tet groups on Ed18.5 and Ed21.5 (84.8%), the incidence between the 2 groups had no statistical significance (P = .642). Lung weight/body weight in the CDH group and the CDH + Tet group were lower than that in the control group (P < .01), and LW/BW in the CDH group was lower than that in the CDH + Tet group (P < .05). Observed under the light microscope and electron microscope, marked hypoplasia of the lungs in fetuses among the CDH groups was observed, in contrast to improvement of the lungs in CDH + Tet fetuses. Statistical differences in morphological parameters (percentage of alveoli area, counting bronchus) were found even on Ed16.5 when diaphragm had not closed (P < .01). The number of type II pneumocytes and lamellar bodies in each group had no significant difference (P > .05). The immunoreactivity of TGF-β1 in CDH group and CDH + Tet group were markedly stronger than that in the control group (P < .01). In addition, TGF-β1 expression in the CDH group was stronger than that in the CDH + Tet group (P < .01).Conclusion
Nitrofen can interfere with lung development early in the fetal rat development before and separate from diaphragm development, and increased expression of TGF-β1 in the lung of CDH rat model may suppress lung growth and development. Prenatal treatment with Tet can improve the growth of the lung of the nitrofen-induced CDH fetuses and its mechanism seems to be involved in downregulating the expression of TGF-β1. It is a likely new approach to treat CDH and its coexistent lung hypoplasia by maternal Tet administration. 相似文献158.
Dai CL Xiong HY Tang LF Zhang X Liang YJ Zeng MS Chen LM Wang XH Fu LW 《Cancer chemotherapy and pharmacology》2007,60(5):741-750
Purpose Tetrandrine (Tet), a multidrug resistant (MDR) modulator, was a potential candidate for use in cancer therapy and exhibited
potent biological activity in vitro and in vivo when combined with anticancer agents such as doxorubicin, paclitaxel. Our
aims were to determine whether serum concentration of Tet, which was capable of blocking P-gp in vitro, could be safely achieved
in mice and whether Tet induced pharmacokinetic alterations in serum doxorubicin disposition in mice.
Methods Tet of 30 mg/kg dose used to reverse MDR was administrated intraperitoneally in mice. Plasma Tet and serum doxorubicin concentration
were analyzed by HPLC. CYP 3A4 activity was examined by HPLC with the substrate of nifedipine.
Results More than 1 μmol/L of Tet could at least tenfold reverse MDR in vitro. The plasma peak concentration of Tet was about 2 μmol/L
and not less than 1 μmol/L until 18 h following Tet administration (i.p.) at 30 mg/kg. These suggested that the concentrations
of Tet that were sufficient to inhibit P-gp might be achieved in mice receiving 30 mg/kg of Tet. Importantly, no significant
difference was demonstrated between the doxorubicin pharmacokinetic parameters obtained in mice received doxorubicin only
and doxorubicin plus Tet. This implied that Tet of 30 mg/kg did not alter the profiles of pharmacokinetics of doxorubicin
including the clearance and AUC of doxorubicin. Furthermore, Tet did not significantly affect on CYP 3A4 activity in human
liver microsomes until more than 25 μmol/L.
Conclusions Tet at the tested dose of combination treatment could achieve plasma concentrations that reversed MDR in experimental models
and it had no apparent effect on doxorubicin pharmacokinetics in mice and CYP 3A4 activity in human liver microsomes.
Chun-Ling Dai and Hui-Yu Xiong equally contributed to this work. Grant support: China National Natural Sciences Foundation
No. 30672407 and Key project Foundation of Guangdong Province No. 2005B10401042 and 985 Key Subject Project Foundation of
State Key Laboratory of Oncology in Southern China. 相似文献
159.
自噬是一种高度保守的溶酶体介导的细胞进程,对维持细胞内稳态具有重要意义,与多种疾病的发生发展密切相关,在肿瘤细胞中具有双重作用。汉防己甲素是从植物中提取的一种双苄基异喹啉类生物碱,在体内外均显示出广泛的抗肿瘤作用,近年来其调节自噬的活性受到了广泛的关注和研究。综述近10年来汉防己甲素在调控肿瘤细胞自噬中的研究进展,为其抗肿瘤作用提供研究思路。 相似文献
160.